GENERAL PHARMACOLOGY

Q: What clinical trial phase do you test on 5000 people? A: Phase III. There are Phases I (25 people/tests safety), II (200 people/tests therapeutic effect), and III (5000 people/compares with other drugs).

Q: Acidic drugs are conjugated to what when excreted? A: Albumin. Basic drugs bind to glycoprotein.

Q: What’s the only inverse agonist we know? A: Antihistamine.

Q: When rating teratogenicity of a drug, D means… A: There is evidence of teratogenicity. There is A, B, C, D, and X. A means no teratogenicity. B means no evidence in humans. C means possible teratogenicity. D has evidence. X is contraindicated in pregnancy.

Q: A drug with an abuse potential of I is… A: highly abusable

Q: What two variables are fixed for drugs? A: Vd (volume of distribution) and CL (clearance)

Q: What kind of Vd does a drug that stays in the plasma have? A: Low Vd.

Q: What circulation does a drug go to if it is absorbed through the middle and inferior rectum? A: Systemic. If superior rectum, goes to portal system.

Q: What blood vessels have M3 receptors? A: vessels used in erection. In all other vessels, sympathetic dominates.

Q: During erection, ACh binds to the M3 on the blood vessels, activating NO Synthase, converting Arginine to NO. What are the steps after this? A: NO activates Guanyl Cyclase, which converts GTP to cGMP, relaxing the smooth muscle and causing vasodilation of vessels in the penis. KNOW THAT cGMP INCREASES!!!

Q: What site on the acetylcholinesterase do ACh and reversible AChEIs bind to? A: They bind to both Esteratic Site (more specifically, on the serine of this site) and the Anionic Site.

Q: What site on the acetycholinesterase do irreversible AChEIs bind to? A: They bind to the Esteratic site only.

Q: What site on the acetylcholinesterase does Pralidoxime bind to? A: They bind to the Anionic Site, kicking the irreversible AChEI poisons off the esteratic site.

Q: What is it called when the irreversible AChEIs bind to the esteratic site too long and loses alkyl groups to become completely irreversible, and not susceptible to pralidoxime antidote? A: Aging. Therefore if it’s too late by the time you treat the poison, you give Atropine only, to help with the cardiovascular symptoms and prevent decrease in heart rate or conduction.

Q: What is the Shortest-acting AChEI and what is it used for? A: Edrophonium (5-15 min), used to diagnose Myasthenia Gravis.

Q: If you wanted to use Edrophonium to treat myasthenia gravis, what other drug do you need to give alongside it?
A: a muscarinic blocker (like atropine), because like carbachol, edrophonium works on both in increasing muscarinic and nicotinic stimulation. Since muscles uses nicotinic, you want to block the muscarinic to prevent decrease in heart rate.

Q: If you have myasthenia crisis, this drug will improve symptoms. If you have cholinergic crisis, it will worsen it. What is it? A: Edrophonium (AChEI). You get cholinergic crisis from overdose of myasthenia gravis treatment.

Q: Which AChEI is lipid-soluble and crosses membranes and therefore can treat glaucoma? A: Physostigmine

Q: Which AChEI is water-soluble and does NOT cross membranes and therefore stay in the muscle and can treat myasthenia gravis? A: Neostigmine, Pyridostigmine.

Q: Hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter… What poisoning am I describing? A: Atropine poisoning — blocks muscarinic, resulting in warm dry skin from decreased sweating/lacrimation/salivation, red from vasodilation, blurry vision from lack of accomodation (ciliary muscle), mad from central nervous effects.

Q: Which anticholinergic drug is used as a preanaesthetic medication to decrease GI and bronchiole secretions before surgery? A: Glycopyrrolate.

Q: What do you use to treat Atropine poisoning? A: Physostigmine (AChEI) –> increases ACh, counteracting ACh receptor antagonism of atropine.Like atropine (mad as a hatter ), Physostigmine is also lipid-soluble and therefore works (vs. Neostigmine, which is NOT lipid-soluble).

Q: Which anticholinergic drug is used to treat motion sickness? A: Scopolamine — blocks mainly M1 (CNS), but can block all M1-3.

Q: What’s the anticholinergic drug that works mainly in bronchioles, and therefore used to treat asthma and COPD? A: Ipratropium. HIGH YIELD!!

Q: What anticholinergic drugs treat overreactive bladder? A: Oxybutynin, Tolterodine, Darifenacin — all synthetic anticholinergic drugs and stop you from peeing that often. (think of an ox peeing by a tollbooth in Darfur)

Q: What M1 antagonists treat Parkinson? A: Trihexyphenidyl, Benztropine (because a decrease in ACh leads to a decrease in GABA, and therefore an increase in DA, which is what Parkinson patients are lacking).

Q: Which cholinergic agonists are not susceptible to AChE? A: Carbachol and Bethanechol. Remember Carbachol works on both Muscarinic and Nichotinic. Bethanechol is agonist for Muscarinic only and is used after surgeries to bring back GI and bladder tone.

Q: Which indirectly-acting adrenergic agonist activates the Radicular Activating System (RAS), keeping you awake, and therefore good for treating Narcolepsy, and increases your focus in ADHD? A: Amphetamine — it is indirectly-acting because it increases NE and DA release, rather than directly bind to sympathetic receptors.

Q: Which drugs will give you postural hypotension as a first dose phenomenon? A: Alpha-1 selective blockers — Prazosin, Terazosin, Doxazosin, Tamsulosin — all the zosin’s

Q: Which alpha blocker can you treat pheochromocytoma? A: Phenoxybenzamine (irreversible, non-selective) — Nowadays, you would use both alpha and beta blocker at the same time, because if you just block alpha receptors, the NE can still work on B1, which can increase HR and cause hypertension. See labetalol and carvedilol.

Q: Which alpha blocker is used to treat Erectile Dysfunction? A: Yohimbine… because it is an alpha-2 selective blocker, which does negative feedback on sympathetic –> increased sympathetic –> ejaculation.

Q: What drugs do you not give diabetes because it blocks their “hypoglycemic warning sign” as well as block glycolysis during hypoglycemia?
A: beta-blockers. hypoglycemia will normally cause fight or flight response to increase glycolysis (B2 action), and doing so, also causes tachycardia (B1 action) which give diabetics a warning. If you give a beta-blocker, you block both of the mechanism of “salvation” and mechanism of “warning,” particularly with drugs that block both B1 and B2 like Propranolol, Nadolol, Timolol, Pindolol, Labetalol, or Carvedilol.

Q: What sympathetic blocker do you NOT use in asthma?
A: the non-selective beta blockers, because they block B2, so your bronchioles can’t dilate.

Q: Which sympathetic blocker gives you rebound hypertension if you skip a dose after chronic use?
A: Propranolol (Clonidine also gives you rebound hypertension but it is an alpha-2 agonist)

AUTONOMICS — MUSCLE RELAXANTS

Q: Which drug is the DOC for Malignant HTN? A: Dantrolene (directly acts on Ca channels), like Malignant HTN caused by Succinylcholine.

Q: What alpha-2 agonist is used as a centrally-acting muscle relaxant? A: Tizanidine

Q: Which type of muscle relaxants are reversed by neostigmine?
A: Non-depolarizing ones, because they are competitive.

Q: Why do you give muscle relaxants via IV?
A: Because they do not cross membranes or BBB — only go to muscle.

Q: Which muscle relaxant do you NOT give people who already have muscle damage (like those who had car accidents)?
A: Succinylcholine — because they are already hyperkalemic. Succinylcholine makes them even more hyperkalemic. Can lead to arrhythmias. Both Hypo and Hyperkalemia can lead to arrhythmias.

Q: Which muscle relaxant can cause apnea if you are pseudocholinesterase deficient?
A: Succinylcholine.

Q: Which muscle relaxant can give you initial fasciculations?
A: Succinylcholine — because it depolarizes.

Q: What drug is contraindicated in Fetal distress, Cephalopelvic Disproportion, and Prematurity? A: Oxytocin — because crosses placenta, you don’t want to give fetus tachycardia. You don’t want to force labor when mother’s pelvis too small, and you don’t want to force labor when the baby’s not ready to come out yet.

Q: What is the adverse effect of Oxytocin? A: Seizures

Q: Vasopressin binds to V1 and V2 receptors. What do they do? A: V1 — vasoconstriction. V2 — inserts aquaporins in renal collecting ducts –> water retention. Both of these actions, of course, increases blood pressure.

Q: Which GnRH analogue is short acting? A: Gonadorelin — so you can use in pulses to induce fertility.

Q: Which GnRH analogue is long acting? A: Leuprolide, Nafarelin, and Goserelin — therefore you can give in continuous dose to inhibit gonadotropin release (but since it’s an analogue, it will have initial transient increased release), Rx prostate cancer, endometriosis.

Q: What drug is used to distinguish Cushing’s Syndrome from ectopic ACTH secretion? A: Corticorelin — a CRH analogue

Q: What is the most potent sulfonylurea? A: Glimiperide, third generation

Q: Which insulin secretagogues do you take with each meal? A: Repaglinide, Nateglinide, Meglitinide — because shorter acting.

Q: Which oral diabetes drug is known to cause hypoglycemia and weight gain? A: Sulfonylureas. In contrast, the other insulin secretagogues (Repaglinide, Meglitinide, and Nateglinide) are more rapid, short-acting, has less weight gain and less hypoglycemia than sulfonylureas.

Q: Which drugs do you use to treat Diabetes with impaired renal function? A: Repaglinide, Nateglinide, Meglitinide — they are insulin secretagogues that have MINIMAL RENAL EXCRETION.

Q: Which diabetes drug does not cause hypoglycemia? A: Biguanides (Metformin) because it just decreases gluconeogenesis.

Q: Which diabetes drug should you NOT use with kidney or liver impairment, or alcohol consumption? A: Metformin, because they can cause additional lactic acidosis.

Q: Which diabetes drug is a GLP-1 analogue? A: Exenatide. It is an incretin –> decreases glucagon release, increases insulin after meals.

Q: Which diabetes drug do you use only as an adjunct? A: Pramlintide — because it’s an amylin analogue, which is an adjuct co-released with insulin. Slows gastric emptying

Q: What can you use to treat beta-blocker overdose? A: Glucagon, because it increases inotropy and chronotropy of heart, without needing to bind the beta-1 receptors (but instead bind glucagon receptors)

Q: Which two types of drugs are insulin sparing (meaning they don’t use insulin at all, and therefore prevents development of insulin resistance)? A: Biguanides (Metformin, which decrease gluconeogenesis), alpha glucosidase inhibitors (Acarbose, Miglitol, which inhibit breakdown of carbs)